An acceleration of expressing many and various genes is observed in inflammation. Such genes include ones encoding interleukin, transcription factors, cohesive molecules, and factors in coagulation system etc. NFκB which is a transcription factor has been said to relate to the transcription of such genes mostly.
It has been known that transcription factor NFκB is expressed in cytoplasm. The transcription and induction of gene due to NFκB-like proteins may be caused by activation of the protein. By such an activation, it becomes possible to translocate the transcription factor prepared in advance from cytoplasm to nucleus.
It is known that this translocation is controlled by phosphorylation and degradation of suppressor protein which is called for IκB.
Transcription factor NFκB was isolated from matured B cells in the form of binding to 10 nucleotide sequence mochief in κ light chain enhancer for the first time. Therefore, NFκB was thought to be specific for the generating stage of matured B cells. However, NFκB-like proteins have been identified in a lot of cells, so it is shown that such a factor relates to induction of gene transcription generally. Such fact has been confirmed by functional identification of an active type NFκB-binding position in some inducing genes.
NFκB is a heterodimer consisting of a submit of 50 kDa (p50) and a submit of 65 kDa (p65).
NF kappa B (NFκB), which is a nuclear factor, is a sequence-specific DNA-binding protein complex which regulates the expression of viral genomes, including the human immunodeficiency virus (HIV), and a variety of cellular genes, particularly those involved in immune and inflammatory responses. The members of the NFκB family in mammalian cells include the proto-oncogene c-Rel, p50/p105 (NFκB1), p65 (RelA), p52/p100 (NFκB2), and RelB etc.
All of these proteins share a conserved 300 amino acid region of homology known as the Rel homology domain (RHD), which is responsible for DNA binding, dimerization, and nuclear translocation of NFκB.
In most cells, Rel family members can form hetero- and homodimers with distinct specificities in various combinations. A common feature of the regulation of transcription factors belonging to Rel family is their sequestration in the cytoplasm as inactive complexes with a class of inhibitory molecules known as IKBs. Treatment of cells with a variety of inducers such as phorbol esters, intedeukin 1, tumor necrosis factor-α (TNF-α), viral infection and many mitogens and cytokines etc. results in the dissociation of the cytoplasmic complexes and translocation of free NFκB into the nucleus. The dissociation of the cytoplasmic complexes is known to be triggered by the phosphorylation and subsequent degradation of the IKB proteins. Such a degradation exposes the nuclear localization sequence in the remaining NFκB heterodimer, leading to nuclear translocation and subsequent binding of NFκB to DNA regulatory elements within NFκB target genes. The p65 submit is frequently detected in NFκB complexes and has a strong transcription activation potential. p65 dimerizes with other NFκB family members and activates gene expression via its potent transactivation domain.